Brain metastases are common in metastatic non-small cell lung cancer (NSCLC) and portend poor outcomes, yet prognostic determinants—particularly whether brain metastases are present at diagnosis or develop during follow-up—remain incompletely characterized in driver-negative patients treated with first-line platinum-based doublet chemotherapy. This retrospective study evaluated prognostic factors affecting overall survival (OS) in patients with metastatic NSCLC who had brain metastases at diagnosis or developed them during follow-up and received first-line platinum-based doublet chemotherapy. A total of 136 epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)-, and c-ros oncogene-1 (ROS-1)-negative patients from a single center were included to identify key demographic, clinical, and treatment-related predictors of survival. Multivariate analysis showed that male sex (hazard ratio [HR]: 2.070), higher Eastern Cooperative Oncology Group (ECOG) performance status (HR: 1.438), presence of multiple metastatic sites (HR: 1.297), and lack of response to first-line chemotherapy (HR: 1.579) were independently associated with worse OS. Conversely, a higher number of chemotherapy cycles was a favorable prognostic factor (HR: 0.797). The timing of brain metastasis, whether present at diagnosis or occurring during follow-up, was not significantly associated with OS. Median OS for the entire cohort was 11.8 months. Females had longer survival than males (21.2 vs. 9.8 months), and patients receiving second-line therapy had improved survival compared with those who did not (24.2 vs. 8.3 months). Survival in this population appears to be primarily influenced by sex, performance status, metastatic burden, and treatment response rather than the timing of brain metastasis.  These findings emphasize the importance of individualized treatment strategies, early response assessment, and access to subsequent therapy.