Purpose: To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials: Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results: The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation).Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3).Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3).Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3).It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions: Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).