Brain radiotherapy (BR) is a well-recognized approach for multiple brain metastases (BMs) from non–small-cell lung cancer (NSCLC). However, the prognosis for these patients remains poor. Apatinib, an antiangiogenic agent targeting vascular endothelial growth factor receptor-2, has shown excellent efficacy in multiple solid tumors. This phase II (WWW. ClinicalTrials.gov Identifier: VEGFR-2 NCT03801200) randomized trial aims to evaluate the efficacy and safety of this combined modality paradigm in patients with BMs from driver mutation-negative NSCLC. The multicenter, open-label, randomized controlled clinical trial. A total of 90 eligible patients were allocated in a 1:1 ratio, to either the experimental group (concurrent lapatinib and BR) or the control group (BR alone). The primary endpoint is intracranial progression-free survival. The secondary endpoints included intracranial objective response rate, intracranial disease control rate, intracranial time to progression, overall survival, and occurrence of peritumoral brain edema using standardized measurement. Quality of life and adverse events were also evaluated.