Patients with 1–3 brain metastases (BM) often receive sterotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT). SRS without WBRT carries a high rate of relapse in the central nervous system (CNS). This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Eligible patients with 1–3 newly diagnosed BM, RTOG RPA class 1–2, received sunitinib after SRS. Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/days 1–28 every 42 days until CNS progression. Neuropsychological testing and MRIs were obtained every two cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS 6 ) after SRS. Fourteen patients with a median age of 59 years were enrolled. Primary cancers included lung 43 %, breast 21 %, melanoma 14 %. Toxicity included grade 3 or higher fatigue in five patients and neutropenia in two patients. The CNS PFS 6 and PFS 12 were 43 ± 14 and 34 ± 14 %, respectively. Of the ten patients who completed >1 neurocognitive assessment, none showed cognitive decline. Sunitinib after SRS for 1–3 BM was well tolerated with a PFS 6 of 43 %. The prevention of progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of BM after definitive local therapy.