Non-contrast CT reliably detects fresh blood in the brain and is the current front-line imaging modality for intracranial hemorrhage such as that occurring in acute traumatic brain injury (contrast ~40-80 HU, size > 1 mm). We are developing flat-panel detector (FPD) cone-beam CT (CBCT) to facilitate such diagnosis in a low-cost, mobile platform suitable for point-of-care deployment. Such a system may offer benefits in the ICU, urgent care/concussion clinic, ambulance, and sports and military theatres. However, current FPD-CBCT systems face significant challenges that confound low-contrast, soft-tissue imaging. Artifact correction can overcome major sources of bias in FPD-CBCT but imparts noise amplification in filtered backprojection (FBP). Model-based reconstruction improves soft-tissue image quality compared to FBP by leveraging a high-fidelity forward model and image regularization. In this work, we develop a novel penalized weighted least-squares (PWLS) image reconstruction method with a noise model that includes accurate modeling of the noise characteristics associated with the two dominant artifact corrections (scatter and beam-hardening) in CBCT and utilizes modified weights to compensate for noise amplification imparted by each correction. Experiments included real data acquired on a FPD-CBCT test-bench and an anthropomorphic head phantom emulating intra-parenchymal hemorrhage. The proposed PWLS method demonstrated superior noise-resolution tradeoffs in comparison to FBP and PWLS with conventional weights (viz. at matched 0.50 mm spatial resolution, CNR = 11.9 compared to CNR = 5.6 and CNR = 9.9, respectively) and substantially reduced image noise especially in challenging regions such as skull base. The results support the hypothesis that with high-fidelity artifact correction and statistical reconstruction using an accurate post-artifact-correction noise model, FPD-CBCT can achieve image quality allowing reliable detection of intracranial hemorrhage.